title: Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia.
abstract: OBJECTIVE
  The development of myeloid malignancies is a concern when administering thrombopoietin receptor (or the myeloproliferative leukemia virus proto-oncogene product, MPL) agonists. Progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia [AML, 9 (6.12%) AML patients among 147 MDS subjects] was reported in a clinical trial. However, only one (0.15%) case of AML among 653 immune thrombocytopenic purpura (ITP) subjects was reported. Our objective was to determine whether there is currently a safety signal in the FDA files termed Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for AML in ITP patients who receive MPL agonists.
  
  
  METHODS
  We conducted a case-controlled study using the FAERS as a source of case and control data. We compared demographic characteristics, such as gender, age and exposure to MPL agonists between AML patients and others among ITP subjects registered between 2002 and 2011.
  
  
  RESULTS
  Total of 4,821 ITP subjects were identified, including 62 AML patients. The number of patients treated with romiplostim and eltrombopag was 54 (1.74%) AML patients among 3,102 ITP subjects and nine (1.52%) AML patients among 594 ITP subjects, respectively. It should be noted that all AML patients were exposed to one or more MPL agonists. Another factor associated with AML was male gender.
  
  
  CONCLUSIONS
  We herein report an association between AML and MPL agonist use in ITP subjects. Due to various biases and the incompleteness of the FAERS data, further studies are warranted to determine whether the detected signal is a real risk. Physicians should not alter their prescribing behaviors based on this single preliminary analysis.
authors.affiliation: Institute of Medical Science, the University of Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oshima
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yuji
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hinomura
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000453:epidemiology; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D013926:Thrombopoietin / Q000009:adverse effects; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim